LINKAGE ANALYSIS IN FAMILIAL DYSPLASTIC NEVUS SYNDROME

摘要黑色素瘤是一种愈来愈常见的皮肤恶性肿瘤，有家族史。 约10%的病例有明显的易感性。家族式的 发育不良痣综合征(FDNS)是一种主要的遗传性疾病 以临床和组织学上不同的黑素细胞为特征 易患黑色素瘤的皮损。先前的努力 为了确定导致这种综合征的基因(S)已经产生 相互冲突的数据。我们建议定义以下链接关系： FDNS的表型和几个候选基因在 皮肤，以努力识别一个或多个可能藏有 这种疾病的原发突变(S)。患有FDN的大型家系 他们将被招募参加这项研究。 将开发新的DNA多态，并与现有的 将确定表皮生长因子的多态、基因类型， 它们的受体和其他候选基因的Southern blotting 和基于聚合酶链式反应的检测。将使用LIPED进行连锁分析 以及相关的计算机程序。建立与一人之间的重要联系 或更多的基因座将形成突变特征的基础 在这些家庭中负责从痣到黑色素瘤的进展。

Melanoma is an increasingly frequent cutaneous malignancy with a familial predisposition evident in about ten percent of cases. The familial dysplastic nevus syndrome (FDNS) is a dominantly inherited disorder characterized by clinically and histologically distinct melanocytic lesions which predispose affected individuals to melanoma. Prior efforts to identify the gene(s) responsible for this syndrome have generated conflicting data. We propose to define the linkage relationships between the FDNS phenotype and several candidate genes which are expressed in skin, in an effort to identify the locus or loci which may harbor the primary mutation(s) in this disorder. Large pedigrees with FDNS have been ascertained, and they will be recruited to participate in the study. Novel DNA polymorphisms will be developed, and together with existing polymorphisms, genotypes will be determined for epidermal growth factors, their receptors, and other candidate loci by means of Southern blotting and PCR-based assays. Linkage analysis will be carried out using LIPED and related computer programs. Establishment of significant linkage to one or more loci will form the basis of characterization of mutations responsible for the progression of nevi to melanoma in these families.